Delayed restoration of lung perfusion after removal of aspirated foreign body.
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Arachis↗
Biomedical subjects
N Kume
Publications and source records attributed to N Kume.
Elevated levels of cAMP inhibit protein kinase C--independent mechanisms of endothelial platelet-derived growth factor-B chain and intercellular adhesion molecule-1 gene induction by lysophosphatidylcholine.
Lysophosphatidylcholine (lyso-PC), a polar phospholipid product increased in atherogenic lipoproteins and atherosclerotic lesions, has been shown to differentially induce functional intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 and mRNA for platelet-derived growth factor (PDGF)-A and -B chains and heparin-binding epidermal growth factor-like growth factor in various cultured endothelial cells. In this study, we have demonstrated increased expression of cell- and matrix-associated forms of PDGF-B chain (PDGF-B) protein elicited by lyso-PC and further characterized potential signal transduction mechanisms responsible for lyso-PC-induced gene expression, focusing on PDGF-B and ICAM-1 genes in cultured human umbilical vein endothelial cell models. Cycloheximide almost completely inhibited PDGF-B but not ICAM-1 mRNA induction elicited by lyso-PC, suggesting that dependence on de novo protein synthesis for PDGF-B is different from that for ICAM-1. Prolonged exposure to phorbol myristate acetate (PMA), which depletes protein kinase C (PKC), or staurosporine, a PKC inhibitor, did not block lyso-PC-induced increases in PDGF-B or ICAM-1 mRNA. Forskolin and dibutyryl cAMP, which elevate intracellular cAMP levels, blocked both PDGF-B and ICAM-1 upregulation elicited by lyso-PC; however, these cAMP-elevating agents did not suppress ICAM-1 upregulation by PMA. Taken together, PDGF-B and ICAM-1 gene induction by lyso-PC may involve different signaling mechanisms; however, both appear to be independent of PMA-regulatable PKC activation but are suppressed by increased levels of intracellular cAMP.
Cells, Cultured↗
[Evaluation of pancreatic cancers using thallium-201 single photon emission computed tomography].
Radionuclide study has not been frequently applied to pancreatic cancers because of the absence of suitable radiopharmaceuticals for their positive depiction. We evaluated thallium-201 chloride (201T1) SPECT for the investigation of pancreatic cancers. The subjects included 24 patients with pancreatic cancer, seven with benign disorders and 10 controls. Each patient fasted prior to the examination for more than 12 hr, and 201T1 SPECT was obtained 10 min after the injection of 148-222 MBq of 201T1. When the boundary of tumor uptake of 201T1 was unclear because of the adjacent physiological liver activity, subtracted SPECT using 99mTc-phytate was performed to clarify it. 201T1 did not accumulate in the pancreas of the controls. In contrast, of the 24 pancreatic cancers, 21 demonstrated positive uptake, for a sensitivity rate of 87.5%, and the mean tumor/liver ratio was 0.76 +/- 0.16 (range, 0.58-1.28). Abnormal uptake was also noted in three of the seven benign disorders, but with a comparatively lower lesion/liver ratio (range, 0.35-0.51). 201T1 activity per mg tissue in the resected specimens of two patients with pancreatic cancer revealed higher activity in the tumor than in normal parenchyma. 201T1 uptake in the five conservatively treated pancreatic cancers showed alteration similar to the serum level of tumor markers. These results suggest that 201T1 SPECT may have clinical potential for investigating pancreatic cancers as well as for the monitoring of treatment effect.
Adenocarcinoma↗
Thallium-201 SPECT and technetium-99m-phytate subtraction liver imaging in the evaluation of pancreatic cancers.
UNLABELLED: We preliminarily evaluated the usefulness of 201Tl SPECT in the investigation of pancreatic cancers. METHODS: The subjects included 32 patients with malignant tumors, 16 with benign disorders and 10 controls. SPECT was performed 10 min after the injection of 148-222 MBq of 201Tl; subjects had fasted to minimize intestinal activity. In addition, subtracted SPECT using 99mTc-phytate to separate the boundary of abnormal uptake from liver activity was carried out in 14 patients. RESULTS: Thallium-201 did not accumulate in the pancreatic bed of the controls. In contrast, 29 of the 32 patients with malignant tumors showed positive phytate uptake with a sensitivity of 90.6% in the detection of malignancy. Of the 16 benign disorders, only four patients showed abnormal uptake; however, the mean value of the lesion-to-hepatic ratio (0.43 +/- 0.06; range, 0.35-0.51), as an index of the degree of uptake, was lower than that in positive malignant tumors (0.72 +/- 0.16; range, 0.53-1.28). Thallium-201 activity per milligram of resected cancer tissue in two patients was 2-3 times greater than in normal tissue. Follow-up 201Tl SPECT in the five treated patients demonstrated similar alterations between 201Tl uptake and tumor markers. CONCLUSION: Our results suggest that 201Tl SPECT may have clinical potential in the investigation of pancreatic cancers.
Adult↗
[Evaluation of regional pulmonary 133Xe-gas washout with dynamic SPECT imaging obtained by a triple-headed SPECT system with continuous repetitive rotating acquisition mode].
The clinical potential of the dynamic SPECT in studying pulmonary washout of Xenon-133 (133Xe), using a triple-headed SPECT system (Toshiba GCA 9300A/HG, Japan) with continuous repetitive rotating acquisition mode, was preliminarily investigated in 6 healthy volunteers and 23 patients with various lung diseases. The equilibrium image was initially acquired for 1 min after breathing 133Xe gas (370 MBq) in a closed circuit for 6 min, and subsequently serial 133Xe-washout SPECT images were continuously acquired every 60 sec for 5-6 min. As the ventilation index, the real half time of regional activity was evaluated. The SPECT study demonstrated the gravity-induced gradient on ventilation in the normal subjects. In the various lung diseases, it allowed us to demonstrate visually and quantitatively the dynamic process and three-dimensional distribution of ventilation abnormalities, with or without chest radiographic abnormalities. These results indicate clinical potential of pulmonary dynamic SPECT of 133Xe-washout for elucidating the distribution and nature of ventilation abnormalities in various lung diseases.
Adult↗
[Regional pulmonary Xenon-133 washout study using dynamic SPECT images obtained by a triple-headed SPECT system].
We investigated preliminary the clinical utility of dynamic SPECT in studying pulmonary Xenon-133 gas washout, using the continuous repetitive rotating acquisition method with a triple-headed SPECT system. The subjects included one healthy volunteer and 16 various lung diseases. After obtaining the equilibrium images, the sequential washout images were acquired every 60 sec for 6 min. As the ventilation index, the real half-time of regional activity was evaluated. With or without abnormalities on chest CT, these images allowed us to show effectively the three-dimensional distribution of ventilation abnormalities, such as peripheral or segmental air trapping.
Humans↗
[Blood flow pattern in pulmonary atelectasis with color Doppler flow imaging].
Blood flow pattern in the lesion was evaluated in 4 patients with pulmonary atelectasis by color Doppler flow imaging synchronized electrocardiography. The pulsatile signal and triphasic signal were detected, whereas the continuous signal was not. It seemed that in pulmonary atelectasis the pulsatile signal was the blood flow signal in the pulmonary artery and the triphasic signal was the blood flow signal in the pulmonary vein.
Aged↗
I-123 IMP scintigraphy in two patients with primary pulmonary malignant lymphoma.
123I-IMP lung scintigraphy was performed in two patients with primary malignant lymphoma, whose radiographic features were difficult to differentiate from inflammatory or atelectatic lesions. 123I-IMP scans revealed a defect in the lesions on the delayed (24 hr) image, suggesting a tumorous lesion. 123I-IMP scan may contribute to differential diagnosis of this rare tumorous entity from benign disorders having a different appearance.
Aged↗
Direct evidence of induction of interdigitated gel structure in large unilamellar vesicles of dipalmitoylphosphatidylcholine by ethanol: studies by excimer method and high-resolution electron cryomicroscopy.
Interaction of large unilamellar vesicle (LUV) of dipalmitoylphosphatidylcholine (DPPC) with ethanol was investigated by the excimer method developed by Yamazaki et al. (Yamazaki, M., M. Miyazu, and T. Asano. 1992. Biochim. Biophys. Acta. 1106:94-98) and the high-resolution electron cryomicroscope with a new cryostage (top-entry superfluid stage) (HiRECM) developed by Fujiyoshi, Y. et al. (Fujiyoshi, Y., T. Mizusaki, K. Morikawa, H. Aoki, H. Kihara, and Y. Harada. 1991. Ultramicroscopy. 38:241-251). The excimer method is based on the fact that the ratio of excimer to monomer fluorescence intensity (E/M) of pyrene PC is lowered in the membrane in the interdigitated gel structure (L beta I), because structural restriction of L beta I structure largely decreases collisions of pyrene rings of the pyrene PCs in the membrane. E/M of pyrene PC in DPPC LUV decreased largely at high concentrations of ethanol, which indicated the induction of L beta I structures in DPPC LUV. Frozen-hydrated DPPC LUVs in a vitreous ice were observed at 4K with HiRECM, and these images were characterized by a pair of concentric circles. The membrane thickness of DPPC LUV which was estimated from the distance between the two concentric lines decreased largely at high concentration of ethanol. The mean value of membrane thickness of the LUV in the absence of ethanol was 3.8 nm, while at 15% (w/v) ethanol was 3.0 nm. These values were almost same as those obtained from the electron density profile of DPPC MLV by the x-ray diffraction analysis in each structures, L beta' and L beta I structures, respectively. These results indicated directly the induction of L beta 1 structure in DPPC LUV at high concentration of ethanol.
1,2-Dipalmitoylphosphatidylcholine↗
Lysophosphatidylcholine transcriptionally induces growth factor gene expression in cultured human endothelial cells.
Lysophosphatidylcholine (lyso-PC) is a major phospholipid component of atherogenic lipoproteins (e.g., oxidized LDL and beta-VLDL) and also can be generated through the action of leukocyte-secreted phospholipase A2 at sites of inflammation. We have previously reported that lyso-PC can activate cultured endothelia, resulting in the selective upregulation of adhesion molecules, such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. In this study, we have found that lyso-PC increased steady state mRNA levels for two smooth muscle/fibroblast-directed growth factors, the A and B chains of PDGF and heparin-binding EGF-like protein (HB-EGF), in cultured human endothelial cells. Lyso-PC did not upregulate the expression of certain other inducible endothelial genes, including E-selectin, IL-8, or monocyte chemoattractant protein-1 in the same cells, in contrast to the coordinate pattern of activation typically observed with other stimuli, such as TNF alpha, bacterial endotoxin, or PMA. Nuclear runoff assays documented an increased transcriptional rate for the HB-EGF gene in lyso-PC-treated cells. Northern blot analyses, after actinomycin D treatment, further indicated that the increased amounts of mRNA for HB-EGF, PDGF A and B chains, and intercellular adhesion molecule-1 were not dependent upon message stabilization. We conclude that lyso-PC can induce growth factor gene expression in cultured endothelial cells and thus may contribute to the migration and proliferation of smooth muscle cells and fibroblasts in various response-to-injury settings in vivo.
Bacterial Toxins↗
Projection structures of human immunodeficiency virus type 1 (HIV-1) observed with high resolution electron cryo-microscopy.
An electron microscopical study was made of human immunodeficiency virus type 1 (HIV-1) in the unstained, frozen, hydrated state at liquid helium temperature. The findings were compared with those obtained from negative staining and ultrathin sectioning. Electron cryo-microscopy confirms and extended the findings obtained by conventional methods. In particular, the virus is shown to be globular, the lipid membrane is clearly resolved as a bi-layer and the bi-layer was demonstrated to be non-uniform in width. The projections studied in the bi-layer are clearly observed to be knob-like and consist of a head, a stalk and a base.
Freezing↗
Technetium-99m-HMPAO as a marker of chemical and irradiation lung injury: experimental and clinical investigations.
UNLABELLED: We evaluated the ability of 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) to serve as a sensitive marker of lung injury. METHODS: Two experimental rabbit models of minimal lung injury were designed using injections of a low dose (0.05 ml/kg) of oleic acid or 50 Gy of irradiation. In addition, we clinically investigated whether patients who received chemotherapy (n = 14) or radiotherapy (n = 13) for lung cancer showed high uptake of 99mTc-HMPAO in the lungs. RESULTS: Despite the minimal endothelial lesions visualized by electron microscopy (edematous changes and blebbing), in both animal models, the lungs showed high uptake of 99mTc-HMPAO, which occurred rapidly within 1 min after injection. Clinically, the mean lung-to-liver ratio of 99mTc-HMPAO activity in the patients who received chemotherapy (0.649 +/- 0.185, p < 0.01) was significantly higher than that of the controls (n = 16; 0.387 +/- 0.108), and all 12 patients who received more than 30 Gy of irradiation showed abnormal uptake in the irradiated lungs, despite the lack of abnormal opacities on chest CT. CONCLUSION: These findings suggest that 99mTc-HMPAO has the potential to be a sensitive marker of chemical and irradiation lung injury.
Adult↗
[Experimental and clinical evaluation of 99mTc-HMPAO as a sensitive marker for chemical lung injury].
To investigate whether 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) can be a sensitive marker of lung injury, an animal model of lung injury was designed in the rabbits using the injection of a low dose (0.05 ml/kg) of oleic acid. In the injured rabbit lungs, electron microscope revealed morphologic changes localized in the microvascular endothelium (edematous change), although their chest radiographies and light microscope did not show any significant changes compared to the controls. In these situations, 99mTc-HMPAO showed a diffusely, high pulmonary uptake, which occurred rapidly within the first 1 min after the injection. Clinically, the lungs in the patients who had been administered with cytotoxic anti-cancer drugs showed a significantly higher 99mTc-HMPAO uptake compared to the controls. These findings indicate that 99mTc-HMPAO may have potential as a sensitive marker of chemical lung injury.
Adult↗
[Difference of thallium-201 kinetics between VX-2 tumors and inflammatory lesions in rabbits].
To evaluate the difference of thallium-201 chloride (201Tl) kinetics between malignant tumors and inflammatory lesions, 201Tl scintigraphy was performed in the 30 rabbits with variable sized VX-2 tumors; and in the 27 rabbits with variable sized inflammatory lesions induced by turpentine oil and the solution of auto-feces. The degree of 201Tl uptake was expressed as the count ratios of the lesions over the contralateral normal muscle tissue, and the early uptake ratio (1 min after the injection) and the delayed uptake ratio (30 min) were acquired. The retention index derived from these ratios was used to assess the degree of 201Tl washout from the lesions. When dividing both the tumors and inflammatory lesions into the large lesions (more than 40 mm in diameter) and smaller ones, different 201Tl kinetics according to the size of the lesions were demonstrated. In the small lesions, the VX-2 tumors showed higher early and delayed uptake ratios and a faster washout than the inflammatory lesions. In contrast, in the large lesions, both the early and delayed uptake ratios were not significantly different; however, the retention index in the tumors was higher compared to the inflammatory lesions. Thus, our animal study indicates that 201Tl kinetics are different according to the size of the tumor and inflammatory lesions, and that in the small lesions the higher tumor uptake compared to the inflammatory lesions may be available to differentiate. However, in the large sized lesions, assessment of the 201Tl washout from the lesions is necessary for differentiation.
Animals↗
Difference in 201Tl accumulation on single photon emission computed tomography in benign and malignant thoracic lesions.
The difference in 201Tl-chloride (201Tl) accumulation on single photon emission computed tomography (SPECT) between 58 benign (58 cases) and 48 malignant (46 cases) thoracic lesions, each of more than 20 mm in diameter was investigated. In the 34 benign and 48 malignant lesions depicted in both early (15 min) and delayed (3 h) images there was no significant difference in the mean early and delayed uptake ratios of lesion to normal contralateral lung between benign and malignant. However, the retention index in the lesion derived from (delayed ratio--early ratio)/(early ratio) x 100% showed a significant difference (benign -4.30 +/- 13.6% versus malignant 23.3 +/- 18.9%, P < 0.01), indicating the poor 201Tl retention in the benign lesions. Using the criteria of nondepiction in the delayed image or a negative retention index, 81.1% accuracy and 95.2% predictive value for diagnosis of benign lesions were obtained. Thus, 201Tl SPECT appears to have potential usefulness in the diagnosis of benign thoracic lesions.
Adenocarcinoma↗
[Evaluation of radionuclide studies in the 8 patients with Takayasu's arteritis].
We evaluated various radionuclide studies performed in the 8 patients with Takayasu's arteritis over the past six years. Radionuclide angiography was performed in 5 patients to investigate the lesions of the branches of the aortic arch, and it demonstrated abnormalities of the affected arteries in 4 patients. Pulmonary perfusion scan demonstrated single or multiple reduced perfusion sites in all the 5 patients examined, while chest radiographies of these patients did not show any abnormalities in the reduced perfusion sites except one case. Renal scintigraphy revealed reduced renal blood flow in 3 patients. In one of those patients, MRI, CT and DSA studies could not detect any stenotic change in the renal artery. Exercise thallium scan revealed myocardial ischemic changes in 2 patients. One of them had angina pectoris, but another patient did not have any complaints. Of the 6 patients who were examined more than one kind of radionuclide studies, five patients showed abnormalities in more than one study. Ambiguous symptoms at the initial stage and rareness of Takayasu's arteritis may delay diagnosis. Radionuclide studies, which can be performed easily and noninvasively to investigate various organs and to depict multiple vascular involvement, seem to be a useful diagnostic tool of this disease.
Adult↗
Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells.
Accumulation of monocyte-derived foam cells in focal areas of the arterial intima is one of the key events in early atherogenesis. We have examined the effect of lysophosphatidylcholine (lyso-PC; lysolecithin), a major phospholipid component of atherogenic lipoproteins, on the expression of adhesion molecules for monocytes, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), in cultured human and rabbit arterial endothelial cells. Cultured rabbit aortic endothelial cells treated with lyso-PC showed increased mRNA and cell surface expression of VCAM-1 and ICAM-1, which was associated with increased adhesion of monocytes and monocyte-like cells (THP-1, U937). In cultured human iliac artery endothelial cells, lyso-PC similarly induced both VCAM-1 and ICAM-1, whereas in umbilical vein endothelial cells only ICAM-1 was up-regulated. In all endothelial cells examined, the effect of lyso-PC on E-selectin (endothelial-leukocyte adhesion molecule-1) expression was negligible, thus differentiating this stimulus from other endothelial activators, such as interleukin 1, tumor necrosis factor, or lipopolysaccharide. We conclude that lyso-PC can selectively induce VCAM-1 and ICAM-1 in arterial endothelial cells and that this action, in addition to its monocyte chemoattractant activity, may play an important role in monocyte recruitment into atherosclerotic lesions.
Animals↗
The role of oxidized lipoproteins in the pathogenesis of atherosclerosis.
1. Oxidized low density lipoprotein (LDL) has been suggested to play an important role in atherogenesis by facilitating the accumulation of lipids in macrophages. In vitro studies from this laboratory have shown that oxidized LDL is recognized not only by the specific receptor for it, but also by the receptor which is common for oxidized LDL and acetyl LDL. Probucol, originally developed as an antioxidant, prevents the oxidative modification of LDL in vitro. Recent studies by the authors show that probucol prevents the progression of atherosclerosis in homozygous Watanabe heritable hyperlipidaemic rabbits in vivo without any changes in plasma LDL cholesterol levels. 2. These results strongly suggest that oxidative modification of LDL could occur in vivo and probucol could slow the progression of atherosclerosis, without changes in plasma cholesterol levels. 3. In addition, recently the authors demonstrated that high density lipoprotein (HDL) particles are also oxidized. Once HDL particles were oxidized, they showed a lessened effect on the decrease of cholesteryl ester in foam cells, suggesting oxidative modification of HDL may stimulate development of atherosclerosis by limiting efflux of cholesterol from foam cells. Moreover, HDL particles from probucol-treated patients are hardly oxidized; subsequently, these HDL particles caused a marked efflux of cholesterol from foam cells.
Animals↗